Alcohol Addiction: A Systems-oriented Approach

Overview

The goal of the multicenter subproject (SP) 10 of the eMED Alcohol Addiction Consortium - A Systems-Oriented Approach is to study neuroimaging x genetics predictions in an existing sample (NGFNplus) of tightly endophenotyped and genome-wide genotyped alcohol dependent subjects (N=240) and controls (N=240); (ii) to translate the results of neuroimaging and genetic analyses from an adolescent risk sample (IMAGEN) to adult disease (NGFNplus sample) by examining related MRI-paradigms tagging the same functional brain systems in both samples (e.g. reward system, inhibitory control system, emotion processing, working memory); (iii) to conduct a follow-up neuroimaging study on the NGFNplus sample validating the neurobehavioral risk profiles predictive for juvenile harmful alcohol use in adult patients with alcohol addiction, (iv) to expand the NGFNplus sample by including a new set of healthy subjects with high genetic risk (1st degree relatives of patients with alcohol addiction). The investigators will do so by using elaborate imaging genetic methods that are already available and successfully used in other multicenter studies by the investigator's research group (e.g. univariate analyses, functional and effective connectivity analyses, polygenetic scores, network topology) as well as by using complex computational algorithms and mathematical models, in particular advanced machine learning methods, developed in SP 6. The investigator's approach aims in the long to predict and characterize longitudinal outcomes in patients with alcohol addiction (5 years following our index session) and to complement the NGFN-sample with an add-on study with 1st degree relatives that will allow the investigators to test the generalizability of the identified predictive risk profiles for early risk identification.

The overall research goal of this project is (i) to study neuroimaging x genetics predictions in an existing sample (NGFNplus) of tightly endophenotyped and genome-wide genotyped alcohol dependent subjects (N=240) and controls (N=240); (ii) to translate the results of neuroimaging x genetic analyses from an adolescent risk sample (IMAGEN) to adult disease (NGFNplus sample) by examining related paradigms tagging the same functional systems in both samples; (iii) to conduct a follow-up neuroimaging study on the NGFNplus sample validating the neurobehavioral risk profiles predictive for harmful alcohol use in adolescents in adult patients with alcohol addiction (iv) to expand the NGFNplus sample by including a new set of healthy subjects with high genetic risk (1st degree relatives of patients with alcohol addiction). The investigators will do so by using imaging genetic methods that are already available and used in other multicenter studies by the investigator's research group (e.g. univariate analyses, functional and effective connectivity analyses, polygenetic scores, network topology) as well as by using computational algorithms and mathematical models, in particular advanced machine learning methods, developed in other sub projects (SPs) of the consortium in particular of SP4 and SP6. The investigator's approach will enable the researchers to characterize outcome longitudinal in patients with alcohol addiction (5 years following our index session) and to complement the NGFN-sample with an add-on study with 1st degree relatives that will allow the investigators to test the generalizability of the identified predictive risk profiles for early risk identification.